apnea (OSA) along with excessive daytime sleepiness (EDS) is termed as
obstructive sleep apnea syndrome (OSAS) or obstructive sleep apnea-hypopnea
syndrome (OSAHS). There are repeated episodes of collapse of upper airway (UA)
The cardinal clinical
symptoms of sleep apnea are 3 S- sleepiness, snoring (often disruptive) and
significant obesity. Another common symptom is large neck circumference (>42
cm in men).
from obstructive sleep apnea complain of daytime sleepiness, poor quality of
life and cardiac, psychiatry and metabolic disorders.
The occurrence of OSA
is 3 percent to 7 percent in males and about 2 percent to 5 percent in females.
The morbidity percentage in obese individuals is 78.
The prevalence of OSA
increases with advancing age and the primary risk factor is obesity.
The criterion of
diagnosis for OSA is either an apnea-hypopnea index (AHI) of more than five
events per hour along with excessive daytime sleepiness or an AHI greater than
15 events per hour irrespective of symptoms. Overnight polysomnography is
needed to calculate the frequency of hypopneic and apneic events.
Peppard et al
conducted a study to assess the relationship between hypertension and
obstructive sleep apnea. They observed that OSA was a risk factor for
hypertension and with continuous positive airway pressure (CPAP), high blood pressure
can be treated.
Marin et al
prospective research found that 'untreated OSA increased the odds by 2.87 for a
fatal and 3.17 for a nonfatal cardiovascular event'.
It was also observed
that OSA may lead to insulin resistance and diabetes.
The treatment for
obstructive sleep apnea (OSA) includes pharmacologic and non- pharmacologic
modalities. Continuous positive airway pressure (CPAP) is the most sought after
treating option for OSA. It is effective in creating a pneumatic splint and
maintaining patency of airway and thus eliminates apnea and hypopnea episodes.
Other therapies are
oral appliances, drug therapy, weight loss and surgery. Reduction of risk
factors, rectifying the underlying metabolic ailments, treating the
repercussions and preventing the episodes of hypopnea and apnea constitute the
goals of the treatment.
improve obstructive sleep apnea by 'increasing rapid eye movement (REM) sleep
latency while decreasing the overall amount of time spent in REM sleep'.
Smith and colleagues
and Brownell et al have studied the effect of Protriptyline as a REM sleep
suppressant. Smith et al revealed that
there was a reduction in snoring and apnea-hypopnea index (AHI) and oxygen saturation
and daytime somnolence improved significantly.
The muscle tone of the
upper airway can be increased by selective serotonin reuptake inhibitors.
Hanzel et al conducted a study that revealed reduction in apnea-hypopnea index
(AHI) from 57 to 34 events per hour with both protriptyline and fluoxetine but
no reduction was noticed in AHI during REM sleep.
'Prasad et al combined
fluoxetine with ondansetron, which yielded small reductions in AHI during
non-REM and REM sleep after 28 days of treatment.'
Nicotine products not
only stimulate respiration but also increase the activity of the muscles
responsible for dilating the upper airway.
'Gothe et al reported that the use of nicotine gum (2 or 4 mg) at
bedtime eliminated obstructive apneas in the first 2 hours of sleep.'
Methylxanthine such as
oral theophylline and IV aminophylline work by inhibiting the adenosine
receptors and stimulates the ventilator drive.
'Mulloy and McNicholas
evaluated oral theophylline for 4 weeks in 12 patients with OSA. They reported
a small yet statistically significant decrease in AHI (from 49 to 40 episodes
per hour) as did Hein et al in a similar study (from 9.2 to 6.7 episodes per
Allergic rhinitis is
known to cause nasal obstruction and deteriorates obstructive sleep apnea.
Inhaled nasal corticosteroids can improve the patency of airway.
'Kiely et al
investigated the use of intranasal fluticasone in 23 snorers with rhinitis for
4 weeks. Further evaluation of the subpopulation of 13 patients with AHI values
above 10 episodes per hour resulted in an observed drop in AHI from 30.3 to
23.3 with the use of inhaled nasal fluticasone.'
The use of oral
leukotriene antagonists such as intranasal budesonide and oral montelukast has
been successful in treating sleep-disordered breathing in children.
'Goldbart et al
studied daily montelukast therapy (4 or 5 mg) in 24 children with OSA for 16
weeks. They reported a significant reduction in respiratory disturbance index
(RDI) and adenoid size.'
decongestants act on the arterioles of the mucosa of nose and result in
vasoconstriction by stimulating alpha-adrenergic receptors.
'Braver and Block evaluated
the use of oxymetazoline in 20 OSA patients, but found it to have no benefit
when used as monotherapy.'
It is seen that
patients with hypothyroidism often suffer from obstructive sleep apnea. This
could be either due to reduction in ventilator drive or weight gain.
therapy may improve the situation however the evidences are quite conflicting.
Menopause or cessation
of menstruation is regarded as a risk factor for sleep-disordered breathing and
snoring. The effects of medroxyprogesterone, estrogen and combination therapy
with progesterone and estrogen on obstructive sleep apnea are also beneficial
in hypercapnia-associated disorders.
such as armodafinil and modafinil have been clinically investigated as
adjunctive therapy for obstructive sleep apnea. The adverse effects are
dizziness, nausea, headache and insomnia.
Sleep apnea can be
treated by additional therapies such as agents for acromegaly, testosterone,
antihypertensives, glutamate antagonists, physostigmine, acetazolamide, opiate
antagonists, tumor necrosis factor (TNF)-alpha agonists, and carbon dioxide
physostigmine, TNF-alpha antagonists, carbon dioxide inhalation and agents for
acromegaly other miscellaneous agents have not been proved to be effective in
lowering OSA symptoms.
'A pilot study of
TNF-alpha agonists did demonstrate reduced AHI and reduced sleepiness, but
further studies would be required to establish their benefit in OSA.'
mirtazapine and donepezil are also beneficial in treating obstructive sleep
apnea. Donepezil is a reversible inhibitor of acetylcholinesterase enzyme, and
is known to improve saturation of oxygen in Alzheimer's patients.
double-blind, placebo-controlled study of donepezil in OSA patients found an
improvement in AHI, oxygen saturation, and REM sleep. The study failed to find
improvement in sleep efficiency or EPSS.'
With increasing doses
of mirtazapine, significant decrease in collapse of upper-airway has been
noticed. However the associated side effects are sedation and weight gain.
apnea can be worsened by CNS depressants such as barbiturates, older sleep
agents, benzodiazepines, opiates and alcohol. These agents can adversely affect
the ventilation control during sleep and make the upper airway easily
Other harmful drugs
such as sildenafil, an erectile dysfunction medication and propranolol, a
beta-blocker should also be avoided in OSA.
It is finally
concluded that clinical trials have failed to reveal noteworthy benefit in
pharmacologic treatment of OSA.
Continuous positive airway pressure (CPAP) still remains a better choice
in comparison to drug therapy.
The researchers said
that further pharmacologic therapies should be formulated for treating daytime
sleepiness and fatigue related to obstructive sleep apnea.
point is the treatment of metabolic disorders and obesity for controlling
patients with OSA.
Pharmacotherapy Options in the Treatment of
Obstructive Sleep Apnea; Kimberly Tackett et al; US Pharm. 2012;37(7):23-26.